59
CHAPTER
Nonepidermoid Cancers of the Head
and Neck
Jerry R Castro, Benjamin R Kummer and Bhuvanesh Singh
Summary
1. Nonepidermoid cancers (NECs) constitute about 10% of all
head and neck cancers.
2. In general, the presentation of NEC is similar to that of
epidermoid cancer, and is driven by the anatomic location of
the tumor.
3. Although arising from the same anatomic locus, the behavior
of head and neck NEC varies by the subsite and
histopathology of the tumor.
4. The parotid is the most common site for salivary gland NEC in
the head and neck.
5. Adenoid cystic carcinomas are the most common type of
minor salivary gland cancer and show a propensity for
perineural spread.
6. Surgery is the treatment of choice for most salivary gland
cancers, with adjuvant radiation in advanced cases.
7. Differentiation is associated with outcome in NEC, with poorly
differentiated small cell carcinomas having the worst
outcome.
8. For melanoma, the poorest prognosis is seen with mucosal-
based tumors.
9. The treatment of lymphoma is primarily nonsurgical.
10. The most common presentation of head and neck lymphoma
is an asymptomatic enlarged lymph node.
INTRODUCTION
Head and neck cancer accounts for slightly more than 6.6% of all
cancers reported in hospital-based registries in the United States (not
including cancers of cutaneous origin).1
There is a wide range of nonepidermoid carcinomas, and they are
most commonly of glandular origin. Less common tumors include
neuroectodermal carcinomas.
The diversity of anatomic loci and tissue types gives rise to a
myriad of different cancers in the head and neck region, including
carcinomas, lymphomas, and sarcomas:
● most are epidermoid in origin, with squamous cell carcinomas
(SCCs) of the aerodigestive tract predominating (85–90%);
● nonepidermoid cancers (NECs) constitute the remaining head
and neck cancers and include nonepidermoid carcinomas (5–7%),
lymphomas (1–3%), and sarcomas (0.7%).
Anatomically, most head and neck cancers arise in the larynx (20.8%),
followed by the oral cavity (17.6%), thyroid (15.8%), and oropharynx
(12.3%) (Table 59.1).1
In general, the clinical presentation of NECs is driven by the
anatomic site of the disease. Common presentations include:
● sinonasal tumors with nasal obstruction, hyposmia, epistaxis, or
an asymptomatic mass or swelling;
● oral cavity and oropharyngeal tumors with dysphagia or odynophagia;
● orbital tumors with proptosis, diplopia or decreased visual
acuity;
● laryngeal tumors with dysphonia, or dyspnea;
● upper esophageal and hypopharyngeal tumors with progressive
dysphagia and weight loss.
There is a wide range of nonepidermoid carcinomas, and they are most
commonly of glandular (salivary and thyroid) origin. Less common
tumors include neuroectodermal carcinomas.
SALIVARY GLAND CARCINOMAS
PREOPERATIVE HISTORY AND
CONSIDERATIONS
Salivary gland cancers account for 3–4% of all head and neck cancers.
The major salivary glands include paired parotid, submandibular and
sublingual glands, and thousands of minor salivary glands line the
upper aerodigestive tract (predominantly in the oral cavity).
Overall, 65–80% of salivary tumors originate from the major sali-
vary glands.2,3 The remaining 20–35% of tumors originate from the
minor salivary glands.4 The distribution of salivary gland neoplasms
is presented in Tables 59.2 and 59.3. The most common tumor of the
salivary glands is epidermoid in origin (mucoepidermoid). Nonepider-
moid carcinomas include adenoid cystic carcinoma, adenocarcinoma,
acinic cell carcinoma, and malignant mixed tumor (Table 59.4).3
Adenoid cystic carcinomas
Adenoid cystic carcinomas represent only 8–10% of all salivary neo-
plasms, but are the most common cancers arising from the subman-
dibular and minor salivary glands. The palate is the most common
site for adenoid cystic carcinomas of minor salivary gland origin, fol-
lowed by the other sites in the upper aerodigestive tract, lacrimal
glands and ceruminal glands in the external ear canal.
Originally called cylindromas based on their histologic appearance,
adenoid cystic carcinomas are now subcategorized into cribriform,
tubular and solid types. A key feature is their propensity for perineural
extension,5 which is often not contiguous. MRI scanning of the cranial
nerve tracts, especially the trigeminal and facial nerves, should there-
fore be obtained as part of a preoperative evaluation. 78
7 Table 59.1 National Cancer Data Base histological types and proportions of head and neck cancers from hospital-based registries.
(Modified from Hoffman et al.1).

Site Number of cases Squamous cell carcinoma (%) Adenocarcinoma (%) Lymphoma (%) Other (%)

Larynx 61 778 93.9 1.4 0.2 4.5

Oral cavity 51 764 86.5 5.2 1.2 7.1
Thyroid 46 648 0.4 92 3.5 4.1
Other 42 553 5.1 1.4 79.8 13.7
Oropharynx 36 271 86.7 2.6 6.8 3.9
Major salivary gland 13 185 16.3 55.4 13.9 14.4
Hypopharynx 12 581 94.9 1.1 0.8 3.2
Eye/adnexa 9 360 10.9 2.1 18 69
Sinonasal 8 932 47.4 13.2 12 27.4
Nasopharynx 7 557 64.2 4 10.2 21.6
Pharynx, NOS 4 393 86 1.8 6.3 5.9
NOS, not otherwise specified

Table 59.2 Distribution of neoplasms in major and minor Adenocarcinomas

salivary glands. Adenocarcinomas are the third most common salivary gland neo-
plasms and are graded histologically into low and high-grade patterns,
Gland Proportion (%) of major or minor which correspond to their biologic behavior:
salivary gland tumors
● low-grade tumors have a well-developed glandular pattern through-
Major salivary glands 65–80% of salivary gland tumors out, very uniform nuclei and minimal mitotic activity;
Parotid 90 ● high-grade tumors have a less developed glandular pattern, nuclear
pleomorphism, and a higher mitotic rate.6
Submandibular glands 10
Adenocarcinomas can arise not only from both minor salivary glands
Sublingual glands <1
but also from the surface epithelium (polymorphous low-grade adeno-
Minor salivary glands 20–35% of salivary gland tumors carcinomas). The histology and basic management are similar.
Although relatively less common in the major salivary glands,
Palate 40–50
adenocarcinomas are the second most common sinonasal malignancy
Sinonasal cavity 10–20 after squamous cell carcinomas.
Sinonasal adenocarcinomas can be divided into three basic clinico-
Tongue 10–15 pathological forms: papillary, sessile, and alveolar-mucoid.7 Although
Cheek/lip 5–10 not uniformly accepted, papillary form (non-colonic-like type) is
thought to have a better prognosis than the sessile form (intestinal
Gingiva, larynx, tonsil, <5 type) or the alveolar-mucoid form.
nasopharynx, pyriform sinus

Acinic cell carcinomas

Acinic cell carcinomas comprise up to 20% of all salivary gland cancers,
arising predominantly in the parotid gland. Bilateral parotid enlarge-
Table 59.3 Proportions of benign and malignant salivary ment can occur in a small number of cases. These tumors tend to be
gland tumors. indolent, with recurrence and/or metastasis occurring in less than 5–
10% of all cases. Overall survival greater than 95% can be expected
Salivary gland Benign (%) Malignant (%) Total (%) with adequate excision.
Parotid 75 25 1965 (70)
Submandibular 57 43 235 (8.4)
Malignant mixed tumors
Malignant mixed tumors can occur:
Minor 18 82 607 (21.6)
● as primary carcinoma (de-novo malignant mixed tumor); or
Total 2807
● arising from a pre-existing pleomorphic adenoma (carcinoma ex-
pleomorphic adenoma).
Pleomorphic adenomas are the most common salivary gland neo-
plasms overall, and less than 5% undergo malignant degeneration. The
88 typical presentation of these cancers is that of a longstanding mass
 Table 59.4 Proportion of malignant neoplasms in different salivary glands.
59
Parotid gland (%) Submandibular gland (%) Minor salivary gland (%)

Mucoepidermoid carcinoma 44 30 25
Adenoid cystic carcinoma 9 36 35
Malignant mixed 17 19 6
Adenocarcinoma 10 7 29
Squamous cell carcinoma 7 6 0
Acinic cell 12 2 1
Other 1 0 4

Total 100 100 100

that shows recent rapid growth. Malignant mixed tumors account for
up to 10% of all salivary gland cancers and mainly arise in the parotid
gland. They are high grade cancers that typically have locally aggressive
behavior and early lymphatic and hematogenous metastasis.
Other salivary gland cancers
Less common salivary gland cancers include:
● epithelial–myoepithelial carcinoma;
● salivary duct carcinomas;
● primary squamous cell carcinomas.
Although epithelial–myoepithelial carcinomas tend to be indolent,
both salivary duct carcinomas and primary squamous cell carcinomas
of salivary gland origin are highly malignant neoplasms. A diagnosis
of squamous cell carcinoma should raise concern for metastatic
involvement of the parotid, especially from a cutaneous primary
tumor.
OPERATIVE APPROACH AND
POSTOPERATIVE CARE
In general, the management of salivary gland cancers involves surgi-
cal excision.
Minor salivary gland cancers
Extirpation of minor salivary gland cancers is based on the location
of the tumor (i.e. partial glossectomy for minor salivary gland cancers
of the tongue). In general, principles of surgery for minor salivary
gland tumors are the same as those for squamous cell carcinomas of
the upper aerodigestive tract.
gland after exiting the stylomastoid foramen. In general, most (>95%)
parotid cancers originate from the superficial lobe.
Given the high rates of failure associated with enucleation and
local excision in general, a superficial parotidectomy is the basic
operation recommended for resection of salivary gland tumors. The
superficial parotidectomy can be extended to remove adjacent involved
structures, including the skin, facial nerve, or deep lobe of the parotid
(Fig. 59.1A–F).
Optimizing outcomes
● Adenoid cystic carcinomas are managed surgically, but
adjuvant radiation therapy should be considered for advanced
stage tumors, perineural extension, and/or inadequate
resection margins. The role for neutron beam therapy is still
emerging for these cancers.
● Treatment of malignant mixed tumors is primarily surgical,
with adjuvant radiation given in advanced stage cases and/or
inadequate surgical margins.
COMPLICATIONS AND SIDE EFFECTS
Adenoid cystic carcinomas
Because of their propensity for perineural extension,5 which is often
not contiguous there is a high rate of treatment failure, even when
pathologically negative margins are achieved.
The natural history for adenoid cystic carcinomas is protracted
with a propensity for slow growth. Even with distant metastases
survival rates are quite good (75–90%) at 5 years. However, overall
survival drops precipitously to about 10–20% by 20 years.

Cancers of the parotid gland

The management of cancers of the parotid gland is based on the extent Tumor type and grade are the most important factors in
of the tumor. Anatomically, the parotid gland resides in the cheek, with determining outcome for most NECs of the head and neck.
its boundaries demarcated by:
● the skin;
● external auditory canal;
● mastoid process; NEUROENDOCRINE MALIGNANCIES
● sternocleidomastoid muscle;
● styloid process and associated musculature; PREOPERATIVE HISTORY AND
masseter;
●
● mandible. CONSIDERATIONS
The parotid is divided into a superficial and a deep lobe based on the The neuroectoderm is the portion of the embryonic ectoderm that
relationship to the facial nerve, which traverses through the parotid gives rise to the central and peripheral nervous system, including 78
7

A B C

D E F
Fig. 59.1 Parotid tumor. A, 73-year-old woman with a longstanding, asymptomatic right parotid tumor. The tumor was first noted 15 years
earlier, and progressively increased in size. B, MRI showing a multilobulated right parotid tumor with central necrosis. C, A modified Blair
incision was marked out on the right side of the neck. Due to the massive size of the parotid tumor, excess expanded skin was anticipated.
Therefore an elliptical excision of skin was incorporated. D, Surgical specimen consisted of a 7 × 8 cm right parotid tumor. E, The surgical
field after a superficial parotidectomy leaving all branches of the facial nerve preserved. F, Bisected specimen showing the tumor to be well-
encapsulated. Final pathology revealed malignant mixed tumor. Postoperative radiotherapy was delivered.

neuroendocrine tissue. Malignancies of neuroectodermal origin are Melanoma

rare, comprising less than 1% of cancers in the head and neck region,
and can be divided into:
● lesions primarily showing epithelial differentiation (group I, neuro-
endocrine carcinomas);
● a non-epithelial neoplasm group (group II).8
Group I tumors
Group I tumors are subgrouped by degree of differentiation, and are
labeled:
● carcinoid (well differentiated);
● atypical carcinoid (moderately differentiated);
● small cell carcinoma (poorly differentiated).9
Most of these tumors arise in the larynx, but can also occur in the
sinonasal cavity, salivary glands and ear. In general, the behavior of
these tumors reflects their differentiation.
Melanoma arises from melanocytes found in the basal layer of the
epidermis, mucous membranes, and retina.
Mucosal-based melanomas have the worst prognosis of any head
and neck site.
The sinonasal tract is the most common location for mucosal
melanomas in the head and neck, followed by the oral cavity.10
● In the nasal cavity, the anterior nasal septum, the lateral nasal wall
and the turbinates are the main subsites affected. Within the
sinuses, melanoma is most often found in the maxillary sinus.
Lymph node metastasis from sinonasal melanoma is uncommon,
and distant metastasis primarily involves the lung and brain.
● In the oral cavity, the upper alveolus and hard palate are the
most frequent subsites affected, and 25% of patients with oral
cavity melanoma are found to have lymph node metastasis at
presentation.
Mucosal melanoma is rare in the nasopharynx and larynx.
There is no formal staging of mucosal melanoma, but most clini-
cians recognize three stages:

Group II tumors ● stage I – localized disease;

● stage II – nodal metastasis;
The group II tumors are more diverse, have predominantly neural
● stage III – distant metastasis.
features and include mucosal malignant melanoma, esthesioneuro-
blastoma, malignant peripheral nerve sheath tumors, and Ewing’s Alternatively, mucosal melanoma can be staged according to the AJCC
90 sarcoma. staging criteria for the site of origin.
 The diagnosis is usually not difficult when the tumor is melanin
rich, but amelanotic lesions can be a clinical challenge. Similar to
cutaneous melanomas, immunohistochemistry for S-100 protein, HMB-
45, and melan-A helps to distinguish melanoma from other tumors.
Esthesioneuroblastoma
Esthesioneuroblastoma (olfactory neuroblastoma) is a malignancy of
neural crest origin arising from olfactory epithelium.11 It occurs over
a wide range of ages from the first to eighth decade of life, with a peak
in the second decade. Symptoms of localized disease include unilateral
nasal obstruction, epistaxis, anosmia, headaches and rhinorrhea.
Symptoms of invasive disease include severe headache, diplopia, or
proptosis. The gross appearance of tumor is a fleshy pinkish gray mass.
Histologically, the most characteristic growth pattern consists of an
intercellular neurofibrillary matrix with clusters of small round-to-oval
cells grouped by vascular septa into lobules.
Radiologic evaluation with CT and MRI helps to stage the
tumor. The most commonly used staging system is the Kadish
classification:
● stage A – confined to the nasal cavity (>90% 5-year survival);
● stage B – extension into the paranasal sinus (80–90% 5-year
survival);
● stage C – extension beyond the sinus (30–50% 5-year survival).
This staging system was modified later to add a stage D – metastasis
to the cervical lymph nodes or distant sites, which occurs in 15–30%
of cases.12
A histologic grading system from Hyams at AFIP is based on degree
of differentiation, cellular anaplasia, and mitotic rate.13 Higher histo-
pathological grade and the presence of metastasis are poor prognostic
factors.
Malignant peripheral nerve sheath tumors
Malignant peripheral nerve sheath tumors (MPNST) are also referred
to as malignant schwannoma, neurofibrosarcoma, neurogenic sarcoma,
neurilemomasarcoma, malignant fibrosarcoma, and malignant neuri-
lemoma.14 Risk factors for development include von Recklinghausen’s
disease and prior radiation therapy. In radiation-induced sarcoma, the
latency period is usually 10–20 years.
A B
Fig. 59.2 Right ethmoid neuroendocrine carcinoma in a 56-year-old man. A&B, CT scans of the sinus revealed a large, heterogeneous soft
tissue mass arising within the right ethmoid sinus and extending to the left ethmoid, right sphenoid, and bilateral frontal sinuses, right orbit
and anterior cranial fossa. C, The patient underwent craniofacial resection, including a right orbital exenteration. The facial incision included
a modified Weber-Fergusson incision with subciliary and supraciliary extension.
Ewing’s sarcoma
Ewing’s sarcoma represents a group of tumors (Ewing tumor of bone,
extraosseous Ewing tumor, primitive neuroectodermal tumor and
59
Askin tumor) characterized by the histological presence of small blue
cells. They have a neural differentiation and contain a reciprocal trans-
location between chromosome 11 to 22 (t[11;22][q24;q12]) that is
pathognomonic.15 Head and neck involvement with these tumors is
extremely rare and usually involves the nasal cavity, paranasal sinuses
or the neck.
OPERATIVE APPROACH AND
POSTOPERATIVE CARE
Group I tumors
Carcinoid tumors
Carcinoid tumors may be locally aggressive, but rarely metastasize
and do well with conservative excision (Fig. 59.2A–C).
Atypical carcinoid tumors
Atypical carcinoid tumors show higher rates of regional and distant
metastasis and aggressive surgical excision is warranted, with adjuvant
therapy used for more advanced disease, albeit with questionable benefit.
Overall survival is moderate for localized disease (up to 80% at
5 years), but much lower with the presence of metastasis.
Small cell carcinomas
Small cell carcinomas are highly aggressive and often associated with
paraneoplastic syndrome and high rates of systemic metastasis to
multiple sites. Despite aggressive chemotherapy, survival is rare
(<5%) at 5 years.
Group II tumors
Melanoma
The recommended treatment for mucosal melanoma of the head and
neck is surgery (Fig. 59.3A–C) with postoperative radiotherapy for
advanced lesions.16,17
C
79
7 Despite aggressive treatment, local control is achieved in fewer
than 50% of all cases. Furthermore, more than 50% of those with local
control of disease ultimately develop distant metastasis. The addition
of radiotherapy to surgery may increase local control, but does not
improve survival due to the development of distant metastasis.
The overall survival rate in patients with mucosal melanoma is
relatively low, ranging from 6–30% at 5 years. The typical natural
history after diagnosis is of multiple recurrences followed by the
development of distant metastases and death. Although two-thirds of
patients will relapse within the first year, it is important to note that
relapses can manifest 10 years or more after initial treatment.
Aggressive surgical resection with a goal of negative margins is
the principle treatment for most nonepidermoid head and neck
neoplasms
Esthesioneuroblastoma
Surgery is the mainstay of treatment and craniofacial resection is the
standard procedure for complete en-bloc resection. Neck dissection is
performed if there is cervical nodal disease.
Adjuvant radiotherapy is generally recommended for improved
disease-free survival, with the exception of Kadish stage A tumors
resected with adequate margins.
The role of chemotherapy is restricted to unresectable, recurrent,
or metastatic disease.
Malignant peripheral nerve sheath tumors
Surgical resection is the mainstay of therapy, with postoperative
radiotherapy recommended because of the propensity for local recur-
rence.
Ewing’s sarcoma
Once nearly universally fatal, survival rates for the Ewing’s group of
tumors has been significantly improved with multidisciplinary man-
agement strategies that include surgery and/or radiation in combina-
tion with systemic chemotherapy.
LYMPHOMA
PREOPERATIVE HISTORY AND
CONSIDERATIONS
Malignant lymphoma represents a neoplastic transformation of cells
that reside in lymphoid tissue. Hodgkin’s disease (HD) is set apart
A B
Fig. 59.3 Malignant melanoma. A&B, 44-year-old man with malignant melanoma lesions of the upper alveolus and hard palate. C, The
patient underwent inferior maxillectomy/palatectomy with placement of an obturator, but developed colonic metastasis 4 years later and
92 died a year afterwards.
from all other types of lymphoma (collectively called non-Hodgkin’s
lymphomas [NHL]).
Hodgkin’s disease is characterized by the presence of Reed-Stern-
berg giant cells. The head and neck region is one of the most common
sites for presentation with HD, followed by mediastinal and para-aortic
nodes. These tumors typically occur in young patients and involve a
single nodal chain. HD rarely involves extranodal sites. It is subdivided
into four histopathological subtypes:
● lymphocyte predominance (4–8%);
● mixed cellularity (20–25%);
● lymphocyte depletion (1–2%);
● nodular sclerosing (65–70%).
In general, the lymphocyte depleted and mixed cellularity subtypes
tend to be more aggressive, while lymphocyte predominance and
nodular sclerosing subtypes tend to be less aggressive. Systemic symp-
toms, including night sweats, fever and weight loss are not uncom-
mon. Overall, 80–90% of patients achieve long-term survival with
modern treatment approaches.18
Although united as NHL, this group of tumors represents a wide
spectrum of diseases with divergent pathogenesis, presentation, course
and outcome. NHL can originate from:
● T cells (30–40% of cases);
● B cells (60–70% of cases);
● NK cells (<5% of cases).
Although the most common presentation is also asymptomatic lymph
node enlargement, NHLs have a higher propensity for involvement of
extranodal lymphatic tissue relative to HD, and this occurs in up to
one-third of cases. Within the head and neck, extranodal sites of
involvement include Waldeyer’s ring (nasopharynx, tonsil and base
of tongue), oral cavity, paranasal sinuses, larynx and, rarely, the
thyroid.
In contrast to HD, NHLs as a group tend towards noncontiguous
nodal and extra nodal dissemination and are subdivided into four
groups based on the Working Formulation.19
● Low-grade malignant lymphomas include small lymphocytic/
chronic lymphocytic leukemia, follicular small cleaved cell, and
follicular mixed small and large cell subtypes. These low-grade
lymphomas have a good prognosis, with 5-year survival ranging
from 60–80%.
● Intermediate-grade lymphomas include diffuse large cell, follicular
large cell, diffuse small cleaved cell, and diffuse mixed small and
large cell subtypes. Intermediate grade lymphomas have a 5-year
survival of 40–55%.
● High-grade lymphomas include large cell immunoblastic, lympho-
blastic lymphoma, and small noncleaved cell (Burkitt’s or non-
C
 Burkitt’s) subtypes. High grade lymphomas have a survival of
25–50%.
Miscellaneous lymphomas include composite, histiocytic, mycosis
Table 59.5 Distribution and frequency of head and neck
sarcomas. (Adapted from Sturgis and Potter,20 Colville et al.,23 59
● Bentz et al.24).
fungoides, and several others.
Histopathology Number Percentage of
total number (%)
OPERATIVE APPROACH AND
POSTOPERATIVE CARE Alveolar soft part sarcoma 6 0.65
Angiosarcoma 114 12.43
The main role of the surgeon in the management of lymphoma is to
establish the diagnosis. Although fine-needle aspiration with immuno- Chondrosarcoma 56 6.11
histochemical and flow cytometry studies can distinguish and subtype Dermatofibrosarcoma protuberans 51 5.56
lymphoma, biopsy of a node or tumor-bearing tissue (tonsil, base of
tongue, nasopharynx, parotid, thyroid) remains the gold standard for Desmoid 2 0.22
establishing a diagnosis. Ewing’s sarcoma 8 0.87
Standard protocols should be followed when performing the biopsy
and the specimen should be sent fresh and sterile to allow for special Fibrosarcoma 38 4.14
studies, including karyotyping and molecular analyses. Hemangiopericytoma 21 2.29
The treatment of lymphoma is primarily nonsurgical, and involves
observation, chemotherapy and/or radiation therapy. Leiomyosarcoma 29 3.16
Liposarcoma 24 2.62
SARCOMA Malignant fibrous histiocytoma 99 10.80
Malignant peripheral nerve 60 6.54
PREOPERATIVE HISTORY AND sheath tumor
CONSIDERATIONS Osteosarcoma 119 12.98
Sarcomas are malignancies of mesodermal origin and are subclassified Primitive neuroectodermal tumor 1 0.11
into soft tissue and bone sarcomas. They are rare, accounting for less
than 1% of all cancer diagnoses in the United States, and only 1% of Retinoblastoma 1 0.11
malignant tumors of the head and neck region.20,21 Rhabdomyosarcoma 99 10.80
Types of sarcomas vary by anatomic subsite in the head and neck:
Synovial sarcoma 39 4.25
● angiosarcomas is the most common in the scalp;
Unclassified/miscellaneous 150 16.36
● fibrosarcoma and malignant fibrohistiocytoma predominate in the
neck, face, and parotid region; Total 917 100

● osteosarcomas is more common in the maxilla and mandible.22

Table 59.5 summarizes the types and frequency of sarcomas in the
head and neck.20,23,24
Pathologic considerations when dealing with sarcoma include the Osteosarcoma
mechanism of growth, tumor size, metastatic potential, and tumor
Osteosarcoma is the most common primary malignancy of bone. It
grade.21
typically occurs in the extremities, but approximately 10% of patients
In general, sarcomas grow in a compressive manner, leading to a
present with a head and neck primary tumor. Most head and neck
pseudocapsule formation. This pseudocapsule is a local inflammatory
cases involve the maxilla (Fig. 59.4) and mandible, but other bony and
response and contains normal tissue mixed with neoplastic cells.
soft tissue sites in the head and neck can also be affected. Head and
Although it is tempting to enucleate the tumor at the pseudocapsule
neck osteosarcomas occur in middle-aged individuals (third to fourth
and not beyond, such treatment will invariably lead to failure.
decades of life), differing from those in the extremities which generally
Within the head and neck, tumor size and location are important
occur in the teenage years. Prior radiation therapy as well inherited
because larger tumors in critical locations can encroach onto critical
factors, such as hereditary retinoblastoma, Li-Fraumeni syndrome,
neurovascular structures, thereby limiting resectability.
and Rothmund-Thomson syndrome, have been associated with an
Overall, nodal metastases are rare, occurring in less than 10% of
increased risk.25
cases. Regional nodal metastasis is more often found in embryonal
rhabdomyosarcoma, synovial sarcoma, epithelioid sarcoma, angiosar-
coma, and malignant fibrous histiocytoma. The most common sites Rhabdomyosarcoma
for distant metastasis include the lung, followed by bone, CNS, and
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma
liver.
of childhood. Overall, it is the third most common extracranial child-
Overall, tumor grade is the most important consideration for prog-
hood solid tumor after neuroblastoma and Wilms’ tumor.26 The sites
nostication and management of sarcomas:
most commonly affected are the head and neck, the genitourinary tract
● high-grade varieties include osteogenic sarcoma, rhabdomyosar- and the extremities. Approximately one-third of all cases occur in the
coma, angiosarcoma, malignant fibrous histiocytoma, malignant head and neck. Of these, approximately:
peripheral nerve sheath tumor, synovial sarcoma, alveolar soft part
● 50% arise in parameningeal sites (middle ear, paranasal sinuses,
sarcoma, and Ewing’s sarcoma;
nasopharynx, infratemporal fossa);
● low-grade, well-differentiated tumors include fibrosarcoma, chon-
● 25% arise in the orbit;
drosarcoma, dermatofibrosarcoma protuberans, desmoid tumors,
and liposarcoma.20,21 ● 25% arise in non-parameningeal sites (Fig. 59.5A–C). 79
7 The International Classification of Rhabdomyosarcomas27 divides
these tumors into pathologic subtypes with prognostic implications:
alveolar RMS is in the poor prognosis category;
● endothelioma, hemangioblastoma, hemangiosarcoma, lymphangio-
● embryonal RMS is in the intermediate prognosis category;
● botryoid RMS and spindle cell RMS are currently considered vari-
ants of embryonal RMS, but are categorized as having a superior
prognosis.
Because the International Classification of Rhabdomyosarcomas is
limited to pediatric patients, pleomorphic RMS is not included in the
classification. Pleomorphic RMS is a high-grade sarcoma that typically
arises in the skeletal muscle of adults. It is an aggressive lesion with
a poor outcome.
Overall, infants and children tend to have embryonal RMS, ado-
lescents and young adults tend to have alveolar RMS, and older adults
tend to have pleomorphic RMS.
Fig. 59.4 Osteosarcoma. A 51-year-old woman with an ulcerated
lesion in the right upper gum and a biopsy showing osteosarcoma.
The patient underwent preoperative chemotherapy followed by a
right extended maxillectomy, skin graft, and placement of an
obturator.
A B
Fig. 59.5 Embryonal rhabdomyosarcoma. A, A 22-year-old man with a 6-month history of a slowly growing ‘parotid tumor’. The patient had
trismus and the mass was fixed. B&C, A CT scan revealed a right masticator space tumor. An incisional biopsy was performed and it
showed embryonal rhabdomyosarcoma. The patient underwent chemotherapy followed by radiotherapy. Several months later, the patient
presented with metastases to the ribs and sacrum.
94
Angiosarcoma
Angiosarcoma (also known as hemangioendothelioma, lymphangio-
sarcoma) typically presents clinically as a red-to-purple, enlarging,
painless, cutaneous lesion in an elderly man (Fig. 59.6).
Histologically, the lesions are usually intermediate to high grade,
and tumors originating in the scalp have a particularly poor prognosis.
The tumors tend to recur locally and metastasize early. As a result,
the 5-year survival is poor, ranging from 12–51%.
Fibrosarcoma
Fibrosarcoma is a malignant tumor of fibroblasts and can be a low- or
high-grade tumor.28
● Low-grade tumors are composed of uniform spindle cells, and they
exhibit rare mitoses, low to moderate cellularity, and a classic
herringbone pattern.
● High-grade lesions have a greater degree of nuclear pleomorphism,
high cellularity, frequent mitoses, and tumor necrosis.
Malignant fibrous histiocytoma
Malignant fibrous histiocytoma (MFH) is the most common soft
tissue sarcoma in adults, with 3–10% occurring in the head and neck.
Head and neck sites include the sinonasal tract, craniofacial bones,
larynx, soft tissue of the neck, major salivary glands, and oral
cavity.29
MFH is an aggressive neoplasm with a tendency towards local
recurrence, and 25–33% of patients developing systemic metastases,
especially to the lung.
Chondrosarcoma
Chondrosarcoma is a malignancy in which tumor cells form cartilage.
It most commonly arises from cartilaginous structures or bone derived
from chondroid precursors, most commonly in the pelvic bones, prox-
imal femur, proximal humerus, distal femur, and ribs. The head and
neck is the site of origin of only 1–12%. The most common head and
neck sites are the jaw bones, paranasal sinuses and nasal cavity,
maxilla and cervical vertebrae.
C

Fig. 59.6 Angiosarcoma. 80-year-old man with a large nasal tumor
3 cm in diameter, reddish and edematous in appearance, biopsy of
which revealed an angiosarcoma.
Subtypes of chondrosarcoma include:
● conventional chondrosarcoma (also termed chondrosarcoma NOS
[not otherwise specified]; the most common subtype);
● clear cell (malignant chondroblastoma);
● myxoid;
● mesenchymal;
● dedifferentiated.
The mesenchymal subtype is an aggressive variant.
Dermatofibrosarcoma protuberans
Dermatofibrosarcoma protuberans (DFSP) is an indolent, low-grade
sarcoma with a locally infiltrative nature. In the head and neck it clas-
sically presents as a slow-growing, painless, firm, solitary subcutane-
ous nodule.
The histologic appearance is a characteristic arrangement of spindle
shaped tumor cells in a cartwheel or whirligig pattern. It is found more
commonly on the trunk (50–60%), followed by the proximal extremity
(20–30%), and the head and neck (10–15%).
OPERATIVE APPROACH AND
POSTOPERATIVE CARE
High-grade tumors are biologically aggressive with a greater meta-
static potential. Low-grade tumors rarely metastasize and are well
managed by surgery, with radiation therapy reserved for locally
advanced tumors.
Osteosarcoma
The use of neoadjuvant chemotherapy beginning in the 1980s revolu-
tionized the management of osteosarcomas, but its role in the manage-
ment of head and neck osteosarcomas has been debated.
● A systematic review of the literature with patients stratified by
margin and adjuvant therapy showed patients with free surgical
margins had better survival if they received chemotherapy.30
● Survival in patients with positive margins was better if they received
chemotherapy, but did not reach the levels seen with adequate
resection.
● In a retrospective review of 44 patients treated in a single institu-
tion, negative surgical margins was found to be the only significant
predictor of overall and disease-specific survival.31
59
The cornerstone for management of osteosarcoma of the head and
neck involves aggressive surgical resection of the primary tumor.
In planning surgery, it is important to appreciate that disease often
extends well beyond radiographically demonstrable changes.
Neoadjuvant chemotherapy should be considered in younger
patients or in cases where initial resection is likely to result in a
positive surgical margin or yield poor functional result.
Adjuvant radiation therapy should be considered after surgical
resection with close or positive surgical margins.
Control rates of more than 70% are now seen with head and neck
osteosarcomas following aggressive treatment.
Rhabdomyosarcoma
Four sequential trials by the Intergroup Rhabdomyosarcoma Study
Group have helped to define the current management of rhabdomyo-
sarcomas. Based on this work, patients with RMS are stratified pre-
operatively and postoperatively.32
Preoperatively, the ‘stage’ of the patient depends on the site of the
primary and TNM classification.
Postoperatively and prior to receiving chemotherapy, the patient
is placed into a clinical ‘group’:
● group I patients have had their primary tumor completely excised
and do not have regional lymph node spread;
● group II patients have undergone complete macroscopic resection,
though final pathology may show microscopic residual disease,
and all have evidence of regional nodal spread;
● group III patients have macroscopic residual disease after
surgery;
● group IV patients have distant metastases at the onset.
Based on stage, group, histology, and age, patients are further strati-
fied into risk groups: low, intermediate, and high, which determine the
adjuvant or neoadjuvant chemotherapeutic regimen administered.
Radiotherapy is part of the rigorous treatment protocol of RMS,
except for clinical group I patients who have embryonal, botryoid or
spindle RMS. Radiotherapy is typically delivered 9–12 weeks after
chemotherapy unless the patient has intracranial extension or cranial
nerve palsy. In these cases, radiotherapy is given concurrently with
chemotherapy.
Angiosarcoma
The mainstay of therapy is surgery, but the addition of radiotherapy
is strongly recommended to maximize the probability of local control.33
Chemotherapy, especially taxane-based treatment, is becoming more
prevalent in treating unresectable or recurrent angiosarcomas.
Fibrosarcoma
Treatment is primarily by wide local excision with negative margins
(Fig. 59.7A&B). Adjuvant radiotherapy or chemotherapy may be
administered in cases that are high grade and in patients with positive
margins.
Malignant fibrous histiocytoma
The treatment of MFH is primarily surgical.
Radiotherapy is used in unresectable cases or if there are close or
positive margins.
Chemotherapy remains investigational and is used mostly for
metastatic disease. 79
7
A B
Fig. 59.7 Fibrosarcoma. A, A 34-year-old woman with a well-circumscribed, firm, tan-gray tumor of the upper alveolus. B, The surgical
specimen after inferior maxillectomy. Histologic examination revealed fibrosarcoma.
Chondrosarcoma
Surgical excision is the primary treatment modality.
Chondrosarcoma is not radioresponsive.34
Dermatofibrosarcoma protuberans
The mainstay of treatment is surgical resection:
● with conservative resection margins, local recurrence rates can be
as high as 60%;
● wide excision (>2 cm) reduces local recurrence to 20%.35
Adjuvant radiotherapy may be useful in cases where a more limited
resection would provide the patient functional and/or cosmetic
benefit.
CONCLUSION
Nonepidermoid cancers of the head and neck encompass a variety of
tumor types with different biological behaviors and include nonepider-
moid carcinomas, lymphomas, and sarcomas.
For many, tumor type and grade is the most important factor
determining outcome. However, tumor size is also important, because
it pertains to overall resectability and morbidity related to sacrifice of
important neurovascular structures.
Aggressive surgical resection with intent to achieve negative
margins is the primary approach for these tumors.
Radiotherapy and chemotherapy are important adjuncts, especially
in cases of extensive disease, high-grade tumor, and a close or positive
margin. Although this may improve disease-free survival in many
patients, the ability of adjunctive therapy to improve overall survival
is limited. Novel combinations and biological agents are being devel-
oped and promise improvements in outcome in the future.
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